Early results from a pilot study into the impact of steroid-toxicity on pediatric lupus nephritis patients suggest that children experience a high burden of steroid-toxicity and that variation in patient susceptibility leads to only a modest correlation between glucocorticoid dose and steroid-toxicity. The results were discussed in a recent webinar hosted by the Steritas team.
Pediatric lupus nephritis is a type of kidney inflammation that affects children with systemic lupus erythematosus (SLE), an autoimmune condition. Glucocorticoids play a key role in pediatric lupus treatment, and dealing with the morbidity associated with long-term steroid exposure remains a central concern for clinicians when thinking about the therapeutic management of these patients.
The study, led by Emily Zhang, BS and Joyce Chang, MD MSCE from Boston Children's Hospital included 45 pediatric patients, with an average age of 13 years. The longitudinal study included data from both prospective patients and retrospective chart review and followed patients who had at least six months of documented glucocorticoid use.
“Treatment options for lupus have expanded significantly in recent years, particularly with the development of adjunctive drug therapies. The hope is that as we integrate these new agents, we can achieve disease control with less reliance on glucocorticoids and, as a result, a reduction in glucocorticoid toxicity.
In order to fully evaluate the benefit and the utility of these new treatments, we can't rely on disease activity as a standalone endpoint for measuring effectiveness. We need to be able to gauge whether or not these adjunctive therapies can limit or even reverse glucocorticoid toxicity - and this is where the pediatric Glucocorticoid Toxicity Index (pGTI) is a game changer,” says Ms Zhang.
The study showed that more than half of the patients had elevated blood pressure, with 11% having a hypertensive episode, and 9% having an episode of PRES (Posterior Reversible Encephalopathy Syndrome). PRES is a rare condition in which parts of the brain are affected by swelling and can cause seizure, severe headache, neurologic deficit and hypertensive emergency.
“With regard to PRES, it's not just hypertension causing it. There is also an inflammatory component, and kids with severe disease have a lot of systemic inflammation. So, when we put these things together, it can generate this increased susceptibility,” comments Dr Chang.
Other toxicities frequently observed were worsening of striae, weight gain (BMI), sleep disturbance and increased infections of Zoster and oral infections, as well as cases of pneumonia that resulted in hospitalization.
Some of the less obvious, but possibly longer lasting side-effects were 13% of patients experiencing impaired or delayed growth and 20% a negative impact on mood.
“I don't think we fully appreciate it or capture it, because there are many things that parents don't necessarily tell us in a one-hour or half-hour visit, but it is a big problem both at home and at school. When you really dig in deep and ask them, parents have significant concerns about anxiety, depression and hyperactivity, and whether their child is going to be able to function in school and have good peer relationships going forward.
These kids are especially vulnerable to peer pressure and adding mood disturbances on top of that makes things very difficult. If we consider how important education is for future health outcomes, parents are right to be concerned,” comments Dr Chang.
The team has been able to expand the patient cohort and collect data from pediatric lupus nephritis patients at Children's Hospital of Philadelphia as well as lupus patients from the Boston Children’s Hospital that don’t have nephritis. They are currently in the process of analyzing data from this multicenter patient cohort.
“We're really excited about the pediatric Glucocorticoid Toxicity Index. We feel that it holds a lot of potential as a clinical endpoint and can be employed in future outcomes research and comparative effectiveness studies. Ultimately, we think that using the pGTI in these contexts will allow us to better understand the utility of new therapies as well as reduce long-term glucocorticoid toxicity,” says Ms Zhang.
Learn more about the devastating effects of steroid-toxicity in children
